A Physiologically Based Modeling Approach to Evaluate Intravenous Levetiracetam Dosing in Term and Preterm Neonates Article Swipe
Alexis M. Johnson
,
Naveen Thomas
,
M. Blumenthal
,
Chrysanthy Ikonomidou
,
Sin Yin Lim
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/jcph.70037
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/jcph.70037
Seizures are the most common neurologic emergency in neonates and are associated with significant morbidity and mortality. Current first‐line pharmacotherapy, phenobarbital, is associated with serious adverse effects, including impairment of the developing brain. Levetiracetam is a well‐tolerated alternative; however, its use is limited because its optimal dosing in neonates remains unknown. Additionally, limited knowledge of levetiracetam pharmacokinetics in neonates, especially preterm neonates, means they generally receive the same weight‐based dosing. This may put preterm neonates at risk of increased adverse events or insufficient drug effects. This study developed a physiologically based pharmacokinetic (PBPK) model for levetiracetam in term and preterm neonates to evaluate their pharmacokinetic differences. After accounting for the physiological changes, a 1.56‐fold increase in drug tissue distribution was needed to represent the increased volume of distribution of levetiracetam in neonates. In term neonates, scaling renal clearance from children based on estimated glomerular filtration rate required a 61% increase to accurately describe renal clearance. Additionally, allometric scaling to extrapolate metabolic clearance required age‐dependent corrections to account for the reduced metabolic clearance. In preterm neonates, extrapolated renal clearance was approximately equal to observed total clearance, suggesting renal clearance as the sole elimination route. Consistently, predicted metabolic clearance approached zero when the postmenstrual age was <37.5 weeks. Our simulations showed that common intravenous levetiracetam dosing regimens resulted in higher plasma concentrations in more premature neonates or those with reduced kidney function. In preterm neonates, these regimens may result in plasma concentrations exceeding toxicity thresholds, indicating a need for lower weight‐based dosing.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/jcph.70037
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jcph.70037
- OA Status
- hybrid
- References
- 84
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4410037883
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4410037883Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/jcph.70037Digital Object Identifier
- Title
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A Physiologically Based Modeling Approach to Evaluate Intravenous Levetiracetam Dosing in Term and Preterm NeonatesWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2025Year of publication
- Publication date
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2025-05-02Full publication date if available
- Authors
-
Alexis M. Johnson, Naveen Thomas, M. Blumenthal, Chrysanthy Ikonomidou, Sin Yin LimList of authors in order
- Landing page
-
https://doi.org/10.1002/jcph.70037Publisher landing page
- PDF URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jcph.70037Direct link to full text PDF
- Open access
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jcph.70037Direct OA link when available
- Concepts
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Levetiracetam, Dosing, Medicine, Pharmacokinetics, Renal function, Volume of distribution, Adverse effect, Anesthesia, Pharmacology, Internal medicine, Epilepsy, PsychiatryTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
- References (count)
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84Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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